NWO Vici grant for atherosclerosis

Prof. Dr. Christian Weber, Director of the Institute for Cardiovascular Prevention (IPEK) in Munich, Germany and holds a professorship at UM’s School for Cardiovascular Diseases (CARIM). He was awarded A NWO Vici grant for his project proposal ‘Putting the brakes on arteriosclerosis’.

Malfunction

A healthy body has a very clever mechanism for clearing out detrimental substances. For instance, if there is too much fat in the blood vessels, white blood cells (macrophages) will actually eat this excess fat. “You can already see this in babies who drink fatty mother’s milk”, says Weber. “If everything goes according to plan, the macrophages simply do their job and then disappear again.”

Macrophages are controlled by chemokines, which are small proteins. The problem arises when these chemokines tell the macrophages to settle in the vascular wall instead of disappearing from the blood vessel. The macrophages form plaques, which may cause clots that roam around through the bloodstream. A blood clot can become so big that it closes off the entire blood vessel, exactly where the plaque is. The consequence: a heart attack, a stroke or a pulmonary embolism. Scientists

have the important task of finding out why those chemokines give off the wrong signals, and how this can be prevented. “Of course you can fight them with antibodies”, Weber suggests, “but this will also affect the good signals that chemokines give off. As a side effect,the immune system will stop functioning. So we’re on the hunt for a treatment that eliminates the bad qualities of the chemokines, but not the good ones.”

Heteromers

There are approximately 50 chemokines. Why so many? Do these proteins all have a specific task or function? Weber and his colleagues published an article on this in the scientific journal Nature Medicine: “Certain chemokines appear to reinforce one another; they have what you might call a synergetic interaction. They form the compound units known as ‘heteromers’. In certain infections, for instance, a cocktail of ten chemokines is active. We focus on these heteromers. First we analyse their structure, then we add peptides. Peptides are molecules that can serve as a building block for proteins. The key is to establish where in the structure those peptides are active. The ultimate goal is to fight and prevent arteriosclerosis.”

Industry

The first results are positive and the industry has shown interest, according to Weber. “We’ve set up a small business called Carolus Therapeutics. It’s important that we capture the peptides in small molecular units, wrapped in a synthetic structure. From there, the step to actually creating a medication is a very

small one. We’re still doing tests on mice, and the preliminary results are looking good. We hope to do our first tests on humans in 2011.”